STUDY: Linnoila, M., I. Saario, and M. Maki. Effect of Treatment With Diazenam or Lithium and Alcohol on Psychomotor Skills Related to Driving: European J. of Clinical Pharm., 7:337-342. 1974.

Site: Department of Pharmacology, University of Helsinki, Helsinki, Finland.

Subjects: Twenty male students, 20 to 23 years old, volunteered. All used alcohol occasionally, none was obese, took drugs, or had any psychiatric disorders.

Method: The double-blind, crossover, 2-week studies under controlled laboratory conditions measured the subacute effects of diazepam alone and in combination with alcohol, and those of lithium alone and in combination with alcohol. The test groups were coded as follows:

Placebo drug, placebo drink

P group

Diazepam, placebo drink

D group

Lithium, placebo drink

L group

Placebo drug, alcohol

A5 group

Diazepam, alcohol

DA5 group

Lithium, alcohol

LA5 group

Testing took place on 7th and 14th days of the treatments. Effects of learning were excluded by allocating subjects at random according to Latin square design. Subjects were trained on apparatus used before the experiments. Each testing period consisted of three sets of tests 30, 90, and 150 minutes after administration of the drug or drink. At each session, half the subjects received alcohol and half, the placebo drink. Changeover of the drinks was done between each session.

Measurements: The subjects assessed their own performance by completing a rating scale that included guessing of the present treatment modality. Psychomotor tests included a choice reaction test, two coordination tests, and an attention test. Blood samples taken at the end of each session were analyzed for lithium (serum, by flame photometry); for diazepam and N-desmethyldiazepam (serum, by electron capture gas chromatography); and for alcohol (blood, method not stated). Test results were treated by a modification (by Fischer) of the analysis of variance using two- and three-factor designs. The attention test results were also examined by the student’s t-test. The three-factor analysis revealed no significant differences among any treatments at the 7th and 14th days; hence, the two-factor analysis was used for presentation.

Subjective assessments: The P and L groups considered themselves normal on the 7th day but impaired on the 14th day during the 15-minute test. Alcohol produced slight subjective impairment at 30 and 90 minutes. Diazepam had no effect. The combined effects of alcohol and diazepam or lithium caused subjective impression of impairment, especially on the 14th day.

On the 7th day, 30 percent of the P group and on 14th day, 50 percent of P group thought they had received a tranquilizer. More than 80 percent of the D group thought their treatment was with a tranquilizer. On the 7th day, 30 percent of the A5 group thought their drink was a placebo and 70 percent of the P group thought they had received alcohol. At the end of the trial (14 days), estimates were 90 percent correct.

Psychomotor measurements: For the choice reaction test, there was no difference between the P and A5 groups. The D group had shorter reaction times and fewer mistakes. The DA5 group was impaired compared to the P group, especially at 30 minutes. Lithium prolonged reaction time and increased mistakes. The LA5 group showed short reaction time and accurate responses at all times.

In coordination test I, alcohol increased the number of mistakes. D subjects had only a slightly increased mistake percentage compared to the P group. The DA5 group had the largest number of mistakes but their percentage of mistakes was of the same order as that for the A5 group. These mistakes increased from 30 to 150 minutes. L subjects had an increased number of mistakes but a low mistake percentage, whereas the LA5 group had a small number of mistakes but an increased mistake percentage.

For coordination test II, the P group had shorter driving times and lower mistake percentages than other groups but their mistake numbers were high. The A5 group showed a lower number of mistakes but an increased mistake percentage and prolonged driving time compared to the P group. At 30 minutes, the results of the P and D groups were similar but at 90 and 150 minutes the mistake percentage of group D increased and their driving time was prolonged. The mistake percentage and driving times were increased in the DA5 group at 30 minutes compared to the P group, but thereafter the DA5 group decreased its mistake percentage and increased its speed. Lithium increased the mistake percentage and prolonged driving times at 150 minutes. The LA5 group showed impairment at every test time compared to the P group.

In the attention test, several groups showed some impairment after alcohol ingestion compared to the P group. The D group did not, but the DA5 group showed impairment at 30 and 90 minutes, the LA5 group showed impairment at 30 minutes, and the L group was generally impaired compared to the P group.

The blood alcohol concentrations of the tested subjects ranged from 0.40 to 0.60 mg/ml, with the highest values being at 90 minutes.

Dosage: Five mg of diazepam were administered three times daily in gelatin capsules; and lithium carbonate tablets were given with dosage adjusted to produce serum concentrations of 0.75 meq/l. Placebos were administered as capsules or tablets identical in appearance to the real items. Alcohol was given in bitters at a dose of 0.5 g/kg; the placebo bitters had the same volume.

Results: The experiments show very little effect of diazepam alone at the chronic dosage given. Alcohol alone caused only a small amount of impairment. The combination of alcohol and diazepam enhanced impairment; interaction may therefore be presumed. Lithium alone caused some impairment, especially in information retrieval, and when combined with alcohol produced a slight antagonism of effects.

Comment: The information is useful but it would be very helpful if experiments with real-world abuse doses of the drugs and alcohol were undertaken first, to be followed by such work as reported here, where the results are quantitatively unimpressive and of uncertain significance with respect to real-world complex performance.

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